American Indians and Alaska Natives (AI/ANs) suffer from marked health disparities when compared to other Americans;mortality rates associated with substance use, accidents, diabetes, homicide, and suicide are unacceptably high. While making health services more accessible is critical in addressing health disparities, mobilizing communities towards healthy living is another important - and often underutilized - tool. This is especially true when we consider the behavioral underpinnings of many health disparities and the potential role of prevention in interrupting the development, among youth, of risk behaviors (e.g., substance use, risky sex, obesity) and in supporting the development of healthy behaviors (e.g., exercise, healthy eating) that can forestall serious health problems in later life. It is becoming increasingly recognized that community involvement is critical in effectively addressing health disparities, with community-based participatory research (CBPR) and Tribal Participatory Research (TPR) methods gaining deserved recognition. Yet most health research is still initiated by academic health centers with little or no community input. We believe that efforts to involve communities in prevention efforts to help their youth develop healthy behaviors and avoid unhealthy choices will be most successful if these methods are fully embraced. Such approaches are particularly well suited for AI/AN communities, especially reservation- or village-based communities defined by both cultural group and location. The Oglala Sioux Tribe (OST) of the Pine Ridge Reservation is a community facing significant health disparities;OST members are among the poorest in our nation with rates of many diseases markedly higher here than in the nation as a whole. Seeking to build on an almost 20-year partnership, researchers at the Centers for American Indian and Alaska Native Health (CAIANH) at the University of Colorado Denver (UCD) and partners within the Oglala Sioux Tribe's Health Administration (OSTHA) seek to transform OST's community research infrastructure through addressing 4 specific aims: 1) To expand and elaborate upon a health research agenda, expected to be initially focused on substance abuse prevention programs for youth;2) to develop bidirectional mechanisms for training the research workforce;3) to cultivate effective dissemination methods for returning research findings to the local community, providing the tribe, other researchers, service providers, and policy makers with the best available information about OST health;and 4) to systematize procedures developed here to provide templates for building sustainable research infrastructure in Native and other communities. The work proposed here builds on the assertive leadership the OSTHA has shown in providing direction and oversight of research and their desire to develop their own research workforce. It also draws on the strengths of seasoned researchers and community advocates in the CAIANH, who have long histories of collaboration with the OST and other AI/AN communities nationwide. PUBLIC HEALTH RELEVANCE: The Oglala Sioux Tribe faces numerous health challenges, many of which are related to behaviors that emerge during childhood and adolescence. This project will solidify the partnership between Centers for American Indian and Alaska Native Health at the University of Colorado Denver and the Tribe's Health Administration, taking concrete steps to build research infrastructure within the Tribe, with a likely focus on prevention activities among the Tribe's youth. It will usher in a new phase in community-based participatory research for health in this community and set a precedent for the development of tribal participation in research in other American Indian and Alaska Native communities as well.